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Blood-Brain Barrier – What Is It?

brain-barrier“Homeostasis” is not a topic commonly discussed at parties or at the dinner table. Nobody pays attention to it unless it’s severely out of order. That’s because few of us know what it is. Your body is able to control everything that goes on inside—the composition of body fluids, the physiological responses to stimuli, the maintenance of body temperature, and whatever else we need to keep equilibrium. That’s homeostasis. Nowhere in the body is it more important than in the brain. The mechanism for supporting this lies in the blood-brain barrier, the BBB. This comprises a network of capillaries that supply blood to the brain. The permeability of these particular capillaries is such that some substances are prevented from entering the brain tissue while others are allowed. Sometimes it’s only a matter of big molecules versus small molecules. The BBB was discovered by a bacteriologist named Paul Ehrlich, who found that a dye injected into the bloodstream colored the tissues of most organs except the brain.

Further study realized that the barrier is located in the endothelial (skin-like) cells of the capillaries, which are joined by tight junctions of substantial electrical resistance, providing a barrier against some molecules. The BBB is both a physical barrier and a system of cellular transport mechanisms. It restricts the passage of potentially harmful materials from the blood, yet allows the traverse of nutrients. Fat-soluble substances, such as ethanol and caffeine, are able to get through by way of the lipid membranes of the cells. Oddly, water-soluble materials, such as sodium and potassium, may not cross the barrier without an escort molecule of some type.

The BBB becomes more permeable during inflammatory attacks, allowing some medications (mostly antibiotics) and phagocytes to pass through. That’s good. A not-so-good thing is that opportunistic bacteria and viruses can get through, too. Most of them are too big, though. Therefore, brain infections are rare. One exception is the spirochete, Borrelia, associated with Lyme’s disease, which seems to be able to infiltrate blood vessel walls after causing inflammation of the central nervous system. (Rupprecht. 2008)  There are very few fat-soluble small molecules that can get through, and that can cause problems when life-saving chemicals are barred entrance. (Pardridge. 2002)  Other than some infectious diseases, no chronic diseases are cured by small-molecule drugs. Large-molecule drugs have the potential to heal patients with neurological conditions, but none can cross the BBB.

INSULTS TO THE BBB

What can harm the blood-brain barrier?  Alcohol, fluoride, oxidized LDL and brain concussions, to name a few.  Alcohol crosses the BBB (Stins. 2009) and forms metabolites that act as signaling molecules to activate enzymes leading to BBB dysfunction and to neuro-inflammatory disorders. (Haorah. 2007)  Furthermore, alcohol causes oxidative neuron damage and results in cognitive deficits that characterize stupor and memory lapses, all because it inhibits the glucose transport upon which the brain depends as a source of energy. (Abdul Muneer. 2011)

As beneficial as topical fluoride might be in the prevention of tooth decay, its ingestion is another story, where elevated levels have been associated with increased rates of mental deficiency and borderline intelligence. Chinese researchers found that high fluoride levels in drinking water have a profound effect on the intelligence of developing children. (Xiang. 2003)  Simultaneous study concluded that fluoride accumulates in the hippocampus—the part of the brain involved in memory—and inhibits activity of cholinesterase, the enzyme that regulates the function of the neurotransmitter, acetylcholine, which mediates synaptic activity. (Zhai. 2003)  In earlier investigations, scientists found that the chemical had impact on those persons chronically exposed to industrial fluoride pollution, wherein there occurred symptoms of impaired central nervous system functioning and faulty cognitions and memories. (Spittle. 1994)  From the outside, fluoride is acceptable treatment for the prevention of caries; from the inside, no.

Oxidized LDL (oxLDL), which appears when LDL spends too much time in the blood before getting repackaged as fat by the liver or being taken up by peripheral tissue, is capable of inducing cell injury. When cerebral endothelial cells are exposed to OxLDL, their viability decreases in a concentration- and time-dependent manner, and their programmed cell death is hastened. Intracellular reactive oxygen species are increased, and mitochondria become dysfunctional. (Chen. 2007)  A blow to the head can cause a concussion, but so can violent jarring or shaking. This sudden change of momentum (the resistance to changes in motion or stability) may evoke unconsciousness or disruption of vital functions of the brainstem. The increased pressure that may result will render the BBB increasingly permeable, particularly at the site of insult. (Beaumont. 2001)

BBB PROTECTION

Is there a way to protect the BBB?  Yes, but there is space here to address only a few. Caffeine—we all know how to get that—has been shown to block disruption of the blood brain barrier in a rabbit model of Alzheimer’s disease (AD). So, what do rabbits have to do with people?  Lab animals are selected based on their organ systems’ similarity of function to corresponding systems in humans. In a cholesterol-induced model of AD, scientists found that caffeine was able to block substances that compromise the integrity of the molecules (called occludins) that hold the tight junctions of the BBB together. (Chen. 20081)  Perhaps caffeine and related drugs may be useful to treat AD. But there’s more. In Parkinson’s disease (PD), similar BBB disruptions are characteristic, and caffeine again was the rescue agent. (Chen. 20082)  (Chen. 2010)

Indian neurologists have studied the effects of curcumin (from turmeric) on patients with AD, and have found the herb’s anti-oxidant and anti-inflammatory properties to be beneficial in treating dementia and traumatic brain injury. The pharmacological effects of curcumin have decreased beta-amyloid plaques, delayed degradation of neurons, and decreased microglia formation while improving overall memory in AD patients. (Mishra. 2008)

Valproic acid (VPA), a histone deacetylase inhibitor, is a drug used to prevent seizures and to stabilize mood, used mostly in epilepsy treatment. Histone acetylation plays an important role in the regulation of gene expression. Keeping it intact is vital. Valproic acid and others of its kind do just that. It protects against cerebral ischemia (decrease of blood supply) and prevents disruption of the BBB. The effects of VPA are mimicked by a companion molecule, sodium butyrate, a compound available as an OTC supplement. (Wang, et al. 2011)  Inflammation and macrophage infiltration follow a cerebral ischemic attack. Injected sodium butyrate or VPA was found to be effective at reducing the area of infarction and inhibiting inflammatory markers, as long as administration occurred within a three-hour window. The potential for use in stroke patients is being studied. (Kim. 2007)

One of the hottest supplements on the market is resveratrol, the magical ingredient in grapes, peanuts and red wine that purports to protect against aging.  Whether it can do that or not is insignificant in light of its use as an anti-mutagenic, anti-inflammatory, and anti-oxidant agent, which render it useful in addressing cardiovascular disease and some cancers. Scientists in Taiwan have found resveratrol to protect the BBB from the damaging effects of oxLDL attack on its tight junctions and the substances responsible for its integrity. (Lin. 2010)  (Chang. 2011)  In normal aging the BBB seems to remain intact, but its permeability becomes an issue. Certain drugs and physical conditions, such as hypertension, may have deleterious effects on its stability. The reactive oxygen species (ROS) spawned by these vehicles can be attenuated by a low molecular weight substance known as alpha-lipoic acid, a sulfurated fatty acid (a thiol) regarded as a member of the B vitamin family and used to metabolize carbohydrates. One of lipoic acid’s claims to fame is the capability to regenerate and to recirculate both the fat-soluble vitamin E and the water-soluble vitamin C, while simultaneously raising intracellular glutathione levels. In this regard it was cited as a meaningful tool in the treatment of oxidative brain damage and neural disorders involving free radicals, such as would arise from ischemia, excitotoxic amino acid brain insult, mitochondrial dysfunction, diabetes and diabetic neuropathy, inborn errors of metabolism and other causes of neural damage. What is deemed the most important thiol anti-oxidant, glutathione, is not usually directly administered, whereas alpha-lipoic acid may be. (Packer. 1997)   Analysis of studies on alpha-lipoic acid finds it to be a participant in processes of cell growth and differentiation, thus adding to its moniker, anti-oxidant of anti-oxidants. (Bilska. 2005)

No mention of anti-oxidants would be complete without vitamin C, the oxidized version of which—dehydroascorbic acid—can cross the BBB via glucose transporters. Though best known for its anti-oxidant powers, vitamin C is also involved in enzyme reactions and the manufacture of collagen in conjunction with amino acids. Because it can traverse the BBB, vitamin C (ascorbic acid) has welcome anti-oxidant potential in the central nervous system. (Agus. 1997). Its use in the treatment of cerebral compression insult, as from a concussion, has preserved BBB integrity and rescued somatosensory function from debilitation. (Lin. 2010)

For years, the failures of clinical trials in the treatment of neurological diseases have been blamed on the tested substances’ ineffectiveness, when the whole time none could get past the blood-brain barrier.

References

Abdul Muneer PM, Alikunju S, Szlachetka AM, Haorah J.
Inhibitory effects of alcohol on glucose transport across the blood-brain barrier leads to neurodegeneration: preventive role of acetyl-L: -carnitine.
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Abraham Al Ahmad, Carole Bürgi Taboada, Max Gassmann and Omolara O Ogunshola
Astrocytes and pericytes differentially modulate blood–brain barrier characteristics during development and hypoxic insult
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D B Agus, S S Gambhir, W M Pardridge, C Spielholz, J Baselga, J C Vera and D W Golde
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Beaumont A, Marmarou A, Fatouros P, Corwin F.
Secondary insults worsen blood brain barrier dysfunction assessed by MRI in cerebral contusion.
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Bilska A, Włodek L.
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Carman Aaron J, Jeffrey H. Mills, Antje Krenz, Do-Geun Kim, and Margaret S. Bynoe
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Chang HC, Chen TG, Tai YT, Chen TL, Chiu WT, Chen RM.
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Mighty Mitochondria… and Cardiolipin, Too

mitochondrion-cross-sectionMitochondria Are…

Suppose you were asked to name the most important part of your car?  Of course, without an engine you’re not going anywhere.  Without a transmission you’re not going anywhere, either.  So, which is it, the engine or the transmission?  Then, once you get moving, it’s nice to be able to stop.  Brakes, right?  Or perhaps you choose to steer around an obstacle.  Maybe there isn’t a most important part.  Ditto the cell, the unit of structure and function of living things, the smallest unit that can perform an essential life process.  Like your car, the cell has parts.  Considering that you have more than fifty trillion cells, the parts have to be tiny, really tiny.

Each cell is enclosed by a membrane that is made from proteins and a double layer of lipids.  The membrane is vital to the existence and function of the cell because it controls the flow of materials into and out of it, and it keeps the cell’s contents from spilling all over the place.  Not only does the cell have a membrane, but also do its components.  If we were to open and stretch out all the membranes of your body, they’d cover more than forty square miles.  But that’s nothing.  If we uncoiled all your strands of DNA and laid them end to end, they’d reach the sun and back more than once.  When the Psalmist said he was fearfully and wonderfully made, he didn’t realize how right he was.

A component of the cell that shares its architecture is the mitochondrion, sometimes referred to as the power plant of the cell because it makes most of the cell’s supply of adenosine triphosphate (ATP), used as a source of chemical energy.  Like the cell itself, the mitochondrion has an inner and an outer leaf to the membrane.  Mitochondria have other tasks besides making energy, including signaling, cell death, and control of the cell cycle. You already know that different cells have different jobs, each determined by what the nucleus says. Some cells do more work than others and require more energy.  Therefore, some have more mitochondria than others.  You would expect to find more mitochondria in a bicep than in the muscle that blinks an eye.  Each mitochondrion has an intermembrane space—found between the outer and inner membrane leaflets—that controls the movement of proteins. Small molecules have no problem crossing the outer membrane, but larger proteins need to be escorted by a specialized signaling sequence. (sorry about the alliteration)  A noted protein that is localized to the intermembrane area is called cytochrome c, the most abundant and stable cytochrome, principally involved in energy transfer.  Mitochondrial proteins vary depending on the tissue.  More than six hundred types have been identified in the human cardiac mitochondria, for example.  And, even though most of a cell’s DNA is in the nucleus, mitochondria have their own supply.

If there were no mitochondria, the higher animals could not exist.  Mitochondria perform aerobic respiration, requiring oxygen, which is the reason we breathe.  Without them we would have to rely on anaerobic respiration, without oxygen.  That process is too inefficient to support us.  Besides, the lack of mitochondria would reduce energy production by fifteen times, which is far too low to allow survival. A mitochondrion’s DNA reproduces independently of the cell in which it is found.  In humans, this DNA covers more than sixteen thousand base pairs, not very many compared to the whole organism.  Mitochondrial DNA holds thirty-seven genes, all of which are needed for normal function.  Thirteen of these supply information for making enzymes involved in oxidative phosphorylation, which is how ATP is made by using oxygen and simple sugars.  The other twenty-four genes help to make transfer RNA (tRNA) and ribosomal RNA (rRNA), which are chemically related to DNA.  These kinds of RNA are responsible for assembling amino acids into functioning proteins.

Mitochondria are passed on through maternal lineage.  Just as a car’s energy supply from gasoline is in the rear, so is a sperm’s mitochondrial energy—in the tail, which falls off after the sperm attaches to the egg.  This means that any problems, like mitochondrial diseases, necessarily come from the female.  Mitochondrial DNA (mtDNA) does not get shifted from generation to generation, while nuclear DNA does.  It is mtDNA that sends some diseases down the line.  mtDNA, though, is also subject to non-inherited mutations that cause diseases.  Fortunately, these are not passed on, but are accountable for various cancers, such as breast, colon, stomach and liver, diseases that have been attributed to reactive oxygen species.  mtDNA has limited capability to repair itself, so the inherited changes may cause problems with the body’s systems, where the mitochondria are unable to provide sufficient energy for cells to do their work.  The inherited consequences may present as muscle wasting, movement problems, diabetes, dementia, hearing loss, or a host of other maladies.

Some mitochondrial functions are performed only in specific cells.  In the liver, for example, they are able to detoxify ammonia, a job that need not be accomplished anywhere else in the body.  Other metabolic tasks of mitochondria include regulation of membrane potential, apoptosis, calcium signaling, steroid synthesis, and control of cellular metabolism.  You can see that mitochondria are vital to life, and their malfunction can change the rules.  In some mitochondrial dysfunctions there is an interaction of environmental and hereditary factors that causes disease.  Such may be the case with pesticides and the onset of Parkinson’s disease—cellular damage related to oxidative stress.  In other dysfunctions, there may be mutations of certain enzymes, such as coenzyme Q10 deficiency, or aberrations in the cardiolipin molecules that are found inside mitochondria, causative of Barth syndrome, which is often associated with cardiomyopathy.  Mitochondria-mediated oxidative stress may also play a role in Type 2 diabetes.  In cases where misconstrued fatty acid uptake by heart cells occurs, there is increased fatty acid oxidation, which upsets the electron transport chain, resulting in increased reactive oxygen species.  This deranges the mitochondria and elevates their oxygen consumption, resulting in augmentation of fatty acid oxidation.  Merely because oxygen consumption increases does not necessarily mean that more ATP will be manufactured, mostly because the mitochondria are uncoupled.  Less ATP ultimately causes energy deficit, accompanied by reduced cardiac efficiency.

Mitochondria can become involved in a vicious cycle of oxidative stress leading to mitochondrial DNA mutations, which leads to enzyme irregularities and more oxidative stress.  This may be a major factor in the aging process.

Rescue My Mitochondria, Please

The neurodegeneration of Parkinson’s disease is characterized by a loss of dopaminergic neurons and a deficit in mitochondrial respiration.  Exposure to some neurotoxins can present with both characteristics.  In a Parkinson’s model provoked by a drug that was produced to mimic the effects of morphine or meperidine (Demerol), but which interferes with oxidative phosphorylation in mitochondria instead, causing depletion of ATP and cell death, scientists at Columbia University’s Center for Neurobiology and Behavior found that the administration of ketone bodies akin to those used in the treatment of epilepsy were able to attenuate the dopaminergic neurodegeneration and motor deficits induced by the drug (Tieu, 2003).  From this and other studies it has been determined that ketones may play a therapeutic role in several forms of neurodegeneration related to mitochondrial dysfunction (Kashiwaya, 2000).

Moving across the mitochondrial membrane, phosphatidylcholine (PC) limits the phospholipid turnover in both the inner and outer leaflets that epitomizes the membrane defect identified in neurological diseases (Dolis, 1996), including Alzheimer’s, a disease in which impairment of mitochondrial function is part of the pathophysiology.  Substances that inhibit mitochondrial function also activate an enzyme called phospholipase A2 (PLA2) that degrades PC in the membrane (Farber, 2000), but reparation to mitochondria may be realized by administering PC liposomes, as evidenced by Russian studies performed in the early 1990s (Dobrynina, 1991).

Cardiolipin is an important component of the inner mitochondrial membrane, where it makes up about 20% of the lipid composition.  Its operational character is critical to the optimal function of numerous enzymes essential to mitochondrial energy metabolism.  Mitochondrial cardiolipin is distinguished from other phospholipids by the presence of linoleic acid derivatives (Schlame, 1990).  The formation of cardiolipin is dependent upon molecules donated by PC, but because it contains 18-carbon fatty alkyl chains with two unsaturated bonds, it bespeaks a linoleic acid heritage.   The need for linoleic acid, an omega-6 fat, was announced by the American Heart Association several years ago (Harris, 2009).

In the aforementioned Barth syndrome there exist cardiolipin abnormalities and resultant defects in the electron transport chain proteins and the architecture of the mitochondrion.   The electron transport chain (ETC) moves electrons from one cytochrome to another during the production of ATP, terminating at oxygen through a series of increasingly strong oxidative activities.  Those few electrons that fail to make it through the entire process leak and form superoxide, a substantially reactive molecule that contributes greatly to oxidative stress and aging.

Since the heart is rich in cardiolipin, it is more than appropriate to maintain its stores.  And linoleic acid is just the thing to do that.  Dutch researchers found that linoleic acid, readily available from sunflower, hemp, grape seed and other oils, restores and even increases cardiolipin levels (Valianpour, 2003).   Chronic over-consumption of omega-3 fats, such as those from fish oils, creates a deficit of omega-6 fats that interferes with the rate of oxygen use by mitochondria, with consequent decrease of cardiolipin (Yamaoka, 1999) (Hauff, 2006).

Coronary heart disease is a major health issue that may be addressed by supporting cardiolipin integrity, but other conditions likewise respond to such support.  Besides maintaining membrane potential and architecture, cardiolipin provides sustainment to several proteins involved in mitochondrial energy production.  If cardiolipin activity is interrupted or deranged, either through oxidative stress or alterations in acyl chain composition, we may anticipate contending with other pathological conditions, such as ischemia and hypothyroidism, and accelerated aging (Chicco, 2007).  These concerns can be allayed by attending to the status of the tafazzin protein that partly underlies cardiolipin metabolism (Xu, 2006).  Superheroes have long been associated with a sidekick, occasionally with role reversal for the nonce.  Working with linoleic acid to bolster cardiolipin is phosphatidylcholine (PC), which assists protein reconstitution by its ability to transfer acyl groups (Xu, 2003) (Schlame, 1991) and enhance protein signaling.  PC exists in every cell of the body, occupying the outer leaflet of the membrane.  Throughout the course of life, PC levels become depleted and may drop as low as 10% of the membrane in elderly people.  Being so, supplementation is warranted, not only to maintain cardiolipin levels and mitochondrial stability body-wide, but also to retard senescence and to improve brain function and memory capacity.

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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Gut Health, Body Health

stomachThe large intestine is seldom the topic of conversation, with the possible exception of surgeons and gastroenterologists. Most “civilians” don’t pay attention to it until it isn’t working right. The inability to move material out of it is one reason. Unusual egesta might be another. Regardless of its laid back persona, the colon is actually an interesting character. It runs from the cecum (the beginning of the large intestine, where the appendix hangs) to the rectum (the dumpster), and extends about five or six feet. If you want to be technical, the colon runs between these two points. The large intestine has no digestive function, but lubricates wastes and absorbs water and remaining salts, and stores useless stuff for eventual removal. It takes about sixteen hours to evacuate the hold. You need to know that the large intestine absorbs vitamins made by colonic bacteria, such as vitamin K and the vitamin A converted from beta-carotene.

Despite that the colon is known for removal of material, there exists inside a raft of bacteria that keep a permanent residence. In fact, there are more bacteria in the colon than cells in the body. If you have ten trillion cells in your body, you have ten times that many microbes, weighing from two to five pounds. This microflora is sometimes called the microbiome or microbiota. Whichever term is used, the activities performed by these bacteria parallel that of an organ, rivaling the metabolic capacity of the liver (MacFarlane, 2010). For example, carbohydrates are fermented to form short-chain fatty acids that support epithelial cell growth, which helps to reduce the absorption of toxic products. The flora recycle carbon and nitrogen, manufacture methane, metabolize steroids, convert lignans and phytoestrogens to other compounds and fight invasion by unwelcome species. Although people can survive without them, these bacteria are among the best of friends. Damaged or abnormal gut flora is the cause of much human agony as a prime factor in disease. Treating the microbiome with dignity and respect may prevent, or even reverse, disorders that include heart disease, autoimmune conditions, allergies and cancer (deVrese, 2008) (Garcovich, 2012).

There are hundreds of different species of micro-organisms living in the gut, more than 95% of which are anaerobic and genetically diverse. A lactobacillus is more different from a bifidobacterium than a human is from a rabbit. Identification of all species is difficult because not all can be cultured, but you can rest assured that your bacteria belong to you, remaining fairly constant throughout your life time. Talk about close friends!  The healthy bacteria provide a natural barrier against pathogenic bacteria, parasites, fungi, viruses, toxins and whatever else would wreak havoc with our health. Basically, there are half a dozen main groups:  Bacteroides, Firmicutes (Clostridia, Lactobacilli, Streptococci), Actinobacteria (Bifido-), Proteobacteria (Entero-), Fusobacteria and Verrucomicrobia. Not all of these offer salubrity. Some are so complex they almost defy taxonomy, but to our benefit, the good control the evil (Vedantam, 2003) (Beaugerie, 2004).

Analyses have determined that specific gut microbes are associated with what we eat. Some are associated with carbohydrates and some with animal proteins, fats and amino acids. It appears they come to the front of the class when it’s their turn to perform. Changing diet from one type of macro-nutrient to another can alter which bacterial strain is on stage at the time. A baby’s gut is clean and sterile until it entertains bacteria from its mother. Vaginal birth may afford bacterial strains directly from mom’s gastrointestinal tract, while caesarean might present strains from the ambient environs, including the air and the attending medical folks. The infant doesn’t establish his own microbiota for up to six months after caesarean delivery, only one month for normal birth. In any case, the microbiota shapes the development of the immune system, and the immune system in turn shapes the composition of the microbiota (Nicholson, 2012).

The influence of gut microbes on immunity is profound and, therefore, associated with long-term health, particularly since microflora is relatively stable throughout adulthood. The dynamics of the gut environment are subject to perturbations, though, such as from stresses or dietary changes. It’s comforting to know that there is considerable interest in developing modalities that can manipulate biome composition to benefit the host through a kind of metabolic communication, such as would affect obesity and type 2 diabetes (Kootte, 2012). In these matters, therapeutic pathways may be designed by enlisting short-chain fatty acids, prebiotics, bile acids and probiotics. Realizing that antibiotics are non-selective in destroying bacteria—they kill the good as well as the bad—this give us the means for resolution of myriad complaints. In general, the host immune system can prevent the overgrowth of pathogens, which, upon ingestion, fall to this complex integrated structure.

Probiotics are helpful in many cases, but are not silver bullets. When used as part of a broad nutritional protocol, they are likely effective in establishing or re-establishing a healthy microbiome. Stress management, elimination of detrimental medications and dietary interventions need to be included in such a protocol. Because they are many and varied in their composition, probiotics are often viewed tentatively until they are administered and monitored for efficacy. Eating fermented foods, like sauerkraut, yogurt and kefir, fosters a nurturing environment for your own microbiome. The florae best known are the Lactobacilli (there are more than 50 strains) and Bifidobacteria (there are more than thirty). Lacto-, in one strain or another, have been used to treat and to prevent a variety of conditions, from bacterial vaginosis to childhood abdominal distress and diarrhea, to childhood respiratory infections. Bifidobacteria comprise about 90% of the intestinal community, and appear in an infant’s gut within days of parturition, especially if breastfed. The Bifido- species has been used to address irritable bowel syndrome, dental caries, blood lipids and glucose tolerance.  A knowledgeable nutrition professional can guide you in the choice of probiotics to meet a specific need if you have one. Oh, yeah, there is a yeast probiotic, called Saccharomyces boulardii, which is quite effective in treating diarrhea associated with antibiotic use, and may even be helpful with Clostridium difficile and acne.

Hey, what about short-chain fatty acids (SCFA), especially butyrate?  We’re glad you asked. Butyrate is derived from the bacterial fermentation of resistant starches and fibers. Its multiple beneficial effects have been demonstrated beyond the colon, mostly because SCFA can be absorbed across the colonic epithelium. Now that gut health has its own fan club, what with renewed interest in the GI barrier defense system, SCFAs are the darlings of moneyed research. These 2-carbons to 5-carbons fatty acids include acetate, propionate, butyrate and valerate, but the 4-carbon butyrate is the featured performer due to its multiplicity of virtues. Among butyrate’s mechanisms of action are the regulation of gene expression, inhibition of histone deacetylase (an action which helps to make copies of DNA), sequestration of ammonia (ammonia causes cloudy thinking), mobilization of renegade fats, and clearance of biotoxins (Soret, 2010) (Fusunyan, 1999) (Yin, 2001). Because butyrate availability in the colon is lower than the other SCFAs, supplementation is highly recommended. You can’t eat enough resistant starches to make enough butyrate to be physiologically significant. However, even at low concentrations, butyrate can inhibit cell proliferation of several colon cancer lines. At high concentrations, it works like gangbusters against cancer cells while leaving healthy cells alone (Omaida, 1996) (Gamet, 1992).

The extraordinary complexity of the human microbiome is only recently revealed, despite having been known for decades. The interdependence between beneficial bacteria and the immune system demands recognition. If the florae can fight the inflammation that threatens them, they can fight whatever threatens their host.

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Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ
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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Colon and Butyrate: The Colon Beyond Punctuation

crammed-jarQuite a lot of people do not like to share their space. It’s understandable that some are uncomfortable when a conversation, as with a stranger, is carried on nose to nose. In Arab countries, it is offensive to step or lean away during such an encounter. There is, however, an instance where closeness cannot be avoided with the microbiome that occupies not only our space, but also us. The human body holds ten times more microbes than human cells, some on the outside, and others on the inside. The skin, the largest organ of the body, houses a range of microbes that live in distinct communities yet work together to protect us from attack by sickness and disease (Grice, 2009). But our attention here is to those on the inside, the microbiota that weigh up to three pounds and contain tens of trillions of members. There might even be more than a thousand different species, about a third of which are common to most of us. The other two-thirds belong only to you.

Though we have a tailor-made personal microbiome, all perform the same physiological functions and have a direct impact on our health. Besides completing digestion by absorbing water and storing wastes, the gut microbes help to make biotin and vitamin K while fighting aggression from the pathogenic gang of bugs and bolstering the immune system. Each of our gut communities remains stable throughout our lives, unless dietary changes are dramatic. Those who consume lots of vegetables and fiber have a different composition from those who live on fatty meats and simple carbohydrates. What happens in the gut telegraphs to what happens in other areas of the body, including areas that manage mood and possibly the onset of chronic and degenerative diseases (Tillisch, 2013).

The neonatal biome starts to form right after birth, when the digestive tract becomes colonized by micro-organisms that come from the mother and from the environment into which it is born. In about three years the biome becomes stable. To keep it that way, we need to take measures that transcend dietary behavior and the mere swallowing of probiotics as adults. Probiotics are micro-organisms. To analogize, they’re like police whose local precinct needs a workplace conducive to efficiency.  If a probiotic, or any array of gut bacteria for that matter, is to augment or to enhance the native population, it needs a favorable place to work. The problem with the typical Western diet is that we feed the upper GI tract without feeding the gut. One way to do that is with resistant starch, the fermentation of which manufactures short-chain fatty acids, notably butyrate. Butyrate nourishes the gut barrier and helps to prevent inflammation.  Very often, however, dietary intake of resistant starch is insufficient to make enough butyrate to be physiologically significant.

What does butyrate do?  It has powerful effects on several colonic functions, not the least of which is the inhibition of inflammation and carcinogenesis, and the reinforcement of the defenses that fight infection and oxidative stress (Hamer, 2008). Butyrate has partners and precursors in the form of acetates and propionates, likewise made by the bacterial fermentation of resistant starch and fiber.  In the company of acetate, butyrate is reported to protect against diet-induced obesity without causing hypophagia, while propionate may reduce food intake. Unfortunately, there is little understanding why this works (Hua, 2012). What distinguishes one from another?  The number of carbons it holds. Acetic acid has two, propionic acid has three and butyric acid has four. The first of these has the scent of vinegar. Propionic acid is found in sweat; butyric acid in rancid butter and vomit.

Butyrate, joined with calcium, magnesium, potassium, sodium or a combination of these minerals inhibits histone deacetylase enzymes, helping butyric acid to enhance the transcription activity of DNA. Sodium butyrate, for example, has been found to increase lifespan in animal experiments (Zhang, 2009). Of the three short-chain fatty acids mentioned, butyrate is more potent than the others at inhibiting invasive colon cancers (Emenaker, 1998). If this activity of the butyrate molecule has been known since the late 1990’s, why has it not received the publicity that newly-concocted drugs, with their hosts of nasty side effects, have?

The reasons for paying attention to your gut go beyond what you read while seated. Some problems can be attenuated with an occasional laxative, although increasing dietary fiber is a better technique. Even the orange-flavored stuff in the plastic canister, used every day, is an improvement. But a butyrate supplement, despite its pungency, is the best thing going, especially as we get older.

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*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.